How to Track Cell Lineages As They Develop

Sequencing and gene-editing advances make tracing a cell’s journey throughout development easier than ever.

Written byKelly Rae Chi
| 8 min read

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HOMING IN ON THE HEART: Using a line of Brainbow mice created for developmental biology studies, researchers label individual cells (green) in the 9.5-day-old mouse embryo. (Blue is a general cell stain, for reference.) A clearing protocol adapted for embryos allows deeper imaging, including zeroing in on the heart as shown here.MINGFU WUThe average human is made up of more than 30 trillion cells, not counting the hefty microbiome he or she carries. Although mostly red blood cells, our bodies comprise about 200 different types of cells. Understanding how organisms grow from one cell type to many different cell types is the overall goal of lineage tracing or fate mapping experiments, the first of which date to the late 19th century.

Historically, cell lineage tracing studies have taken large pools of cells from mature tissues and inferred their origins retrospectively by staining the cells with vital dyes or transplanting isotopically labeled cells into donor animals. In the past few years, however, an ever-expanding set of tools for single-cell analysis has allowed researchers to track each cell’s fate as it happens—by focusing on embryonic development in animal models or by tracking the differentiation of specific populations of stem cells. For example, researchers can now use combinations of transgenic animal models and modern imaging techniques to view single cells buried deep within embryos. And next-generation sequencing, in particular, RNA sequencing, allows researchers to delineate changing patterns of gene expression as new cell types form. Lastly, the CRISPR-Cas9 system ...

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